Cystic Fibrosis (CF) and Chronic Renal Failure (CRF) are two major, usually fatal diseases of increasing national concern. Each of these disorders results in a generalized disturbance in fluid metabolism which is reflected in abnormal secretions formed by the exocrine sweat gland. For years, a NaCl concentration in the sweat greater than 70 mM/liter has been characteristically diagnostic of CF in children. Recently, we (Prompt, et al., 1976) have determined that the sweat from patients in CRF is significantly elevated in concentrations of alkali cations (Ca and Mg) and phosphate. In Cystic Fibrosis a defect in the fluid transport properties of CF exocrine glands may be basically responsible for the progressive complications of this disease. It has not been possible to rigorously evaluate the characteristics of affected tissues because pathological specimens to which classical physiological techniques might be applied have not been sufficiently accessible or available. In CRF, disorders in extrarenal organs are likely to be secondary to renal dysfunction. Presently, we lack an explanation for the elevated concentrations of divalent ions found in sweat from CRF patients. Knowledge of sweat gland function in CRF disease is virtually non-existent. In the hope of defining fluid management abnormalities in these diseases, we have developed novel preparations for carrying out investigations which heretofore have not been feasible. For the first time we have: 1) a method to study the secretory function of single exocrine sweat glands in vitro, 2) the capability to microperfuse and collect from isolated segments of sweat gland tubules, and 3) the technology to analyze the elemental composition of ultra-microsamples acquired in the above preparations. With these tools in hand we propose to define the properties of stimulation-response, active transport, and permeability associated with fluid movements in normal sweat glands and in glands from CF and CRF patients with the objective of defining generalized defects in these diseases and of expanding our knowledge of exocrine gland physiology.